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As one of just two NCI-designated Comprehensive Cancer Centers in Virginia, VCU Massey Cancer Center is at the forefront of the nation’s cancer research efforts. Researchers at Massey conduct laboratory-based basic, population, and clinical and translational-focused research to advance improved approaches to prevent, diagnose and treat cancer. Continue reading to learn more about publications from Massey researchers in May and June 2023.

PUBLISHED RESEARCH

Targeting a specific gene could enhance multiple myeloma treatment

Massey research member: Steven Grant, M.D.
Journal: Cellular Oncology
Publication date: May 1, 2023

The ATR enzyme plays a critical role in the DNA damage response to single-strand DNA breaks and replication stress. Multiple myeloma has been shown to be particularly susceptible to replication stress and ATR inhibition. Through a recent study, VCU scientists set out to characterize the interactive relationship between ATR and the STAT3 gene in human multiple myeloma cells. Their findings demonstrate a previously unidentified role for ATR in activating STAT3 in multiple myeloma, and suggest that STAT3 inactivation contributes to the efficacy of ATR inhibitors in this disease.

VCU collaborators: Xiaoyan Hu, Ph.D.; Lin Li, Maciej Kmieciak, Ph.D.; Hashim Mann, M.D.; Jewel Nkwocha; Kanika Sharma; and Liang Zhou

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Concurrent dose-finding of a novel cancer drug with and without a second agent

Massey research member: Nolan Wages, Ph.D.
Journal: Journal of Clinical and Translational Science
Publication date: May 10, 2023

More complex research questions are being posed in early-phase oncology clinical trials, necessitating design strategies tailored to contemporary study objectives. This manuscript highlights an example of a novel application to augment future innovative design implementation and demonstrate adaptive designs’ flexibility in satisfying dynamic conditions.

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Protein promotes lung disease in chemo-damaged tissue

Massey research member: Eddie Chae, Ph.D.
Journal: The American Journal of Pathology
Publication date: May 30, 2023

Bleomycin (BLM) sulfate is an antibiotic often used as a chemotherapy drug. Findings from a recent study indicate that BLM-induced lung injury significantly elevated the presence of the DKK1 protein in the lungs in mice, consistent with lung tissues from pulmonary fibrosis patients. These results demonstrate that DKK1 promotes inflammation and fibrosis upon BLM-induced lung injury, suggesting it could be an effective therapeutic target for pulmonary inflammation and tissue repair.

VCU collaborators: Eun-Ah Sung; Min Hee Park; and Patricia Sime, M.D., FRCP

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Oral bacteria offer potential clues for pancreatic cancer treatment

Massey research member: Jose Trevino, M.D., FACS
Journal: Microorganisms
Publication date: May 31, 2023

Poor oral health and the loss of teeth have long been associated with the development of pancreatic cancer. Through a recent study, researchers explored the relationship between the oral and tumor microbiomes of patients diagnosed with pancreatic cancer. They identified a high prevalence and abundance of a common bacteria found in the mouth, gut and vaginal cavity across all cancer patients and sample types. These findings may lead to a potential target to ultimately improve patient outcomes in this deadly disease.

VCU collaborators: Devon Freudenberger, M.D.; and Vignesh Vudatha, M.D.

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Researchers evaluate risk factors in cancer patients during COVID-19 pandemic

Massey research members: Victor Yazbeck, M.D.; and Dipankar Bandyopadhyay, Ph.D.
Journal: Cancer Investigation
Publication date: June 5, 2023

The cancer population is significantly impacted by COVID-19 due to inherent risks of infection imposed by their disease and treatments. Through a recent study, Massey researchers evaluated risk factors in cancer patients in an effort to inform improved guidelines for cancer treatment during a COVID-19 pandemic. The study determined that delaying cancer therapy during peak infection is likely not necessary, and improved knowledge in the risks of infection and utility of personalized precautions can better prepare providers and patients for another potential wave of COVID-19.

VCU collaborators: Patrick Willard, D.O.; Edem Defor; Yiwei Hang; and Temitayo Olasehinde

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Researchers identify effective drug combinations in breast cancer

Massey research members: Chuck Harrell, Ph.D.; and Mikhail Dozmorov, Ph.D.
Journal: Cancers
Publication date: June 14, 2023

ER-positive breast cancer is the most diagnosed subtype of breast cancer. Patient outcomes have improved in recent years, but many tumors will develop resistance and recur as endocrine-therapy-resistant metastases. Through a recently published study, Massey researcher Chuck Harrell, Ph.D., identified two drugs that when paired with the hormone therapy tamoxifen effectively inhibited breast cancer growth better than either drug or tamoxifen alone.

VCU collaborators: Emily Zboril; David Boyd; Alex Duong; Madelyn Esquivel; Andrea Ferreira-Gonzalez, Ph.D.; Jacqueline Grible, Ph.D.; Nicole Hairr; Tess Leftwich; Amy Olex; and Scott Turner, Ph.D.

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Catheter-based therapy boosts survival in subset of liver cancer patients

Massey research member: Andrew Poklepovic, M.D.
Journal: Journal of Gastrointestinal Oncology
Publication date: June 30, 2023

Yttrium-90 (Y90) radioembolization is a catheter-based therapy for hepatocellular carcinoma, the most common form of liver cancer. A recent retrospective study aimed to evaluate the clinical effectiveness of Y90 and long-term impact on patients' liver function. Findings from the study demonstrate that Y90 can be used safely with promising survival rates in properly selected patients.

VCU collaborators: Hannah Lee, M.D.; Laura Alder; Sean Dougherty; Matthew Nguyen; Yuesheng Qu, M.D.; and Leroy Thacker, Ph.D.

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PUBLISHED REVIEWS

The role of polo-like kinase 1 in regulating the forkhead box family transcription factors

Massey research member: Zheng Fu, Ph.D.
Journal: Cells
Publication date: May 8, 2023

Polo-like kinase 1 (PLK1) is a serine/threonine kinase with more than 600 phosphorylation substrates through which it regulates many biological processes. In this review, researchers discuss PLK1-mediated regulation of the FOX family of transcription factors (FOX TF), highlighting the effects of PLK1 on the activity and stability of these proteins. They reviewed the prognostic and clinical significance of these proteins in human cancers and, more importantly, the different approaches that have been used to disrupt PLK1 and FOX TF-mediated signaling networks. Furthermore, they discuss the therapeutic potential of targeting PLK1-regulated FOX TFs in human cancers.

VCU collaborators: Xavier Moore; and Lilia Gheghiani, Ph.D.

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Advances in Hodgkin’s lymphoma pharmacotherapy: A focus on histone deacetylase inhibitors

Massey research member: Victor Yazbeck, M.D.
Journal: Expert Opinion on Pharmacotherapy
Publication date: June 2, 2023

Classical Hodgkin lymphomas (cHL) usually have excellent cure rates. Yet, for patients with refractory or relapsed cHL, prognosis deteriorates as the disease becomes resistant to therapies. Through a recent review, scientists believe that HDAC inhibitors — given their disease control capacity, synergistic interaction with currently approved drugs and ability to overcome drug resistance, particularly PD-1 inhibitors — will eventually become incorporated into the treatment of cHL.

VCU collaborators: Thuy Ho, M.D.; Cara Coleman, M.D.; and Palak Shah, M.D.

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Sex differences in lung cancer

Massey research members: Joseph Landry, Ph.D.; and Patrick Nana-Sinkam, M.D.
Journal: Cancers
Publication date: June 8, 2023

Lung cancer remains one of the most commonly diagnosed cancer in the U.S., only behind sex-specific cancers such as breast and prostate cancer. While not a sex-specific cancer, lung cancer exhibits sex-specific trends. This narrative review focuses specifically on these biological differences and their contributions to this difference. Gaining a better understanding of the biological reasons behind this sex difference could lead to better treatment and screening decisions in the clinic that take the biological sex of the patient into consideration.

VCU collaborators: Lauren May; and Howard Li, M.D.

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Targeting epidermal growth factor receptor for cancer treatment: Abolishing both kinase-dependent and kinase-independent functions of the receptor

Massey research member: Yuesheng Zhang, M.D., Ph.D.
Journal: Pharmacological Reviews
Publication date: June 20, 2023

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is activated by ligand binding, overexpression or mutation. It is well known for its tyrosine kinase-dependent oncogenic activities in a variety of human cancers. A recent review discusses emerging experimental therapeutics that have shown potential of overcoming the limitation of the current EGFR inhibitors in preclinical studies. The findings underscore the importance and feasibility of targeting both kinase-dependent and -independent functions of EGFR to enhance therapeutic efficacy and minimize drug resistance.

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Secondary-type mutations in acute myeloid leukemia: Updates from ELN 2022

Massey research members: Steven Grant, M.D.; and Keri Maher, D.O.
Journal: Cancers
Publication date: June 22, 2023

Therapeutic advances in acute myeloid leukemia (AML) are dependent on identifying and targeting the molecular aberrations that drive disease. The European Leukemia Net (ELN) 2022 guidelines have improved the categorization of AML into distinct molecular subgroups. This review provides a background and foundation for rational molecular-based therapeutic approaches and combination strategies to inspire future clinical trial designs.

VCU collaborators: Ian Bouligny, M.D.

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Written by: Blake Belden